Is metronidazole (Flagyl) safe to use during the 2nd trimester of pregnancy?

Metronidazole Safety in the Second Trimester of Pregnancy

Metronidazole is safe to use during the second trimester of pregnancy and is recommended for appropriate indications after the first trimester. 1

Safety Profile and Recommendations

• Metronidazole is classified as FDA Pregnancy Category B, indicating that animal reproduction studies have not demonstrated fetal risk, but there are no adequate well-controlled studies in pregnant women 2
• The drug is contraindicated during the first trimester but is considered safe for use after this period 1
• The CDC guidelines support metronidazole use in the second trimester as it does not represent a major teratogenic risk 1

Evidence Supporting Safety

• Prospective controlled cohort studies have confirmed that metronidazole does not represent a major teratogenic risk in humans when used in recommended doses 3
• A large study following 228 women exposed to metronidazole in pregnancy (86.2% with first-trimester exposure) found no difference in the rate of major malformations compared to controls (1.6% vs. 1.4%) 3
• Historical data from 597 pregnant women treated with standard courses of oral metronidazole showed no increased incidences of low birth weight, stillbirths, or congenital abnormalities compared to untreated women 4

Dosing Recommendations for Second Trimester Use

For trichomoniasis:

• 2g orally in a single dose 1

For bacterial vaginosis:

• 500mg orally twice daily for 7 days (preferred regimen) 1
• Alternative: 250mg orally three times daily for 7 days 1

Important Precautions

1. Avoid alcohol: Patients should avoid alcohol during treatment and for 24 hours afterward to prevent disulfiram-like reactions 1

2. Breastfeeding considerations: Metronidazole is secreted in human milk in concentrations similar to plasma. A decision should be made whether to discontinue nursing or the drug, considering the importance of the drug to the mother 1, 2

3. Monitoring: For high-risk pregnant women, follow-up evaluation 1 month after treatment completion is recommended to evaluate treatment effectiveness 1

Potential Concerns

• Some research suggests that metronidazole as the sole antibiotic in the second trimester might be associated with a higher rate of preterm delivery in high-risk populations 5
• A randomized controlled trial (PREMET Study) found that metronidazole did not reduce early preterm birth in high-risk pregnant women and may have increased preterm delivery rates 6

Clinical Decision-Making Algorithm

1. Confirm indication: Ensure appropriate diagnosis (trichomoniasis, bacterial vaginosis, or other approved indication)
2. Verify trimester: Confirm patient is in second trimester (metronidazole is contraindicated in first trimester)
3. Select appropriate regimen: Choose recommended dosing based on indication
4. Counsel patient: Advise on alcohol avoidance and potential side effects
5. Schedule follow-up: Especially important for high-risk pregnant women

Conclusion

The evidence strongly supports that metronidazole is safe for use during the second trimester of pregnancy when clinically indicated. While some studies have raised concerns about potential associations with preterm birth in high-risk populations, the overall safety profile is favorable, and the drug remains recommended by the CDC for appropriate indications after the first trimester.